Cyclophilin a inhibits human Respiratory Syncytial Virus (RSV) replication by binding to RSV-N through its ppiase activity

Wenzhang Liang, Yue Zhang, Miao Li, Fadhl Al-Shaebi, Jian Li, Jing Zhang, Lin Wei

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Human respiratory syncytial virus (hRSV) is the most common pathogen which causes acute lower respiratory infection (ALRI) in infants. Recently, virus-host interaction has become a hot spot of virus-related research, and it needs to be further elaborated for RSV infection. In this study, we found that RSV infection significantly increased the expression of cyclophilin A (cypA) in clinical patients, mice, and epithelial cells. Therefore, we evaluated the function of cypA in RSV replication and demonstrated that virus proliferation was accelerated in cypA knockdown host cells but restrained in cypA-overexpressing host cells. Furthermore, we proved that cypA limited RSV replication depending on its PPIase activity. Moreover, we performed liquid chromatography-mass spectrometry, and the results showed that cypA could interact with several viral proteins, such as RSV-N, RSV-P, and RSV-M2-1. Finally, the interaction between cypA and RSV-N was certified by coimmunoprecipitation and immunofluorescence. Those results provided strong evidence that cypA may play an inhibitory role in RSV replication through interaction with RSV-N via its PPIase activity. IMPORTANCE RSV-N, packed in the viral genome to form the ribonucleoprotein (RNP) complex, which is recognized by the RSV RNA-dependent RNA polymerase (RdRp) complex to initiate viral replication and transcription, plays an indispensable role in the viral biosynthesis process. cypA, binding to RSV-N, may impair this function by weakening the interaction between RSV-N and RSV-P, thus leading to decreased viral production. Our research provides novel insight into cypA antiviral function, including binding to viral capsid protein to inhibit viral replication, which may be helpful for new antiviral drug exploration.

Original languageEnglish (US)
Article numbere00563-21
JournalJournal of virology
Volume95
Issue number15
DOIs
StatePublished - Aug 2021
Externally publishedYes

Keywords

  • CSA
  • CypA
  • PPIase
  • RSV-N
  • Viral replication

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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